PACKAGE LABEL - PRINCIPAL DISPLAY PANEL

Indications and Usage for Albumin (Human)

Hypovolemia

Albumin (Human) 20% is indicated in the emergency treatment of hypovolemia with or without shock. Its effectiveness in reversing hypovolemia depends largely upon its ability to draw interstitial fluid into the circulation. It is most effective in patients who are well hydrated. When blood volume deficit is the result of hemorrhage, compatible red blood cells or whole blood should be administered as quickly as possible. [1, 2]

When hypovolemia is long standing and hypoalbuminemia exists accompanied by adequate hydration or edema, 20% - 25% albumin solutions should be used. [ 1 ]

Hypoalbuminemia

For subjects with hypoalbuminemia who are critically ill and/or are bleeding actively, Albumin (Human) 20% infusions may be indicated. [ 3 ] When albumin deficit is the result of excessive protein loss, the effect of administration of Albumin (Human) 20% will be temporary unless the underlying disorder is reversed.

Prevention of Central Volume Depletion after Paracentesis due to Cirrhotic Ascites (Treatment Adjunct)

Albumin (Human) 20% may be used to maintain cardiovascular function following the removal of large volumes of ascitic fluid after paracentesis due to cirrhotic ascites. [ 2 ]

Ovarian Hyperstimulation Syndrome (OHSS)

Albumin (Human) 20% may be used as a plasma expander in fluid management relating to severe forms of ovarian hyperstimulation syndrome (OHSS). [7, 8]

Adult Respiratory Distress Syndrome (ARDS) (Treatment Adjunct)

Albumin (Human) 20% infusions may be indicated in conjunction with diuretics to correct the fluid volume overload associated with ARDS. [ 5 ]

Acute Nephrosis (Treatment Adjunct)

Albumin (Human) 20% may be used to treat edema in patients with acute nephrosis who are refractory to cyclophosphamide and corticosteroid therapy. [ 1 ]

Hemolytic Disease of the Newborn (HDN)

Albumin (Human) 20% is indicated in the treatment of hyperbilirubinemia. It may be used prior to or during an exchange procedure in an attempt to bind free and to enhance its removal. [ 6 ]

Albumin (Human) Dosage and Administration

Dosage

General Recommendations

The concentration of the albumin preparation, dosage and the infusion rate should be adjusted to the patient’s individual requirements.

The dose required depends on the body weight of the patient, the severity of trauma or illness and on continuing fluid and protein losses. Measures of adequacy of circulating volume and not plasma albumin levels should be used to determine the dose required.

The daily dose should not exceed 2 g of Albumin (Human) 20% per kg of body weight.

Hypovolemia

In adults, an intravenous infusion of 25 g should be given. If adequate response (stabilization of circulation) is not achieved within 15 to 30 minutes, an additional dose may be given.

In spite of limited information about the efficacy in pediatric subjects, an intravenous infusion of 2.5 to 12.5 g or 0.5 to 1 g/kg body weight may be given. If adequate response (stabilization of circulation) is not achieved within 15 to 30 minutes, an additional dose may be given.

Hemodilution may follow administration of Albumin (Human) 20%. If hemorrhage has occurred, this may result in relative anemia. This condition should be controlled by the supplemental administration of compatible red blood cells or compatible whole blood.

Hypoalbuminemia

In adults, intravenous infusion of 50 to 75 g of Albumin (Human) 20% may be used. Hypoalbuminemia is usually accompanied by a hidden extravascular albumin deficiency of equal magnitude. This total body albumin deficit must be considered when determining the amount of albumin necessary to reverse the hypoalbuminemia.

In burns, therapy usually starts with the administration of large volumes of crystalloid injection to maintain plasma volume. After 24 hours, Albumin (Human) 20% may be added at an initial dose of 25 g with the dose adjusted thereafter to maintain a plasma protein concentration of 2.5 g per 100 mL or a serum protein concentration of 5.2 g/100 mL.

Prevention of Central Volume Depletion after Paracentesis due to Cirrhotic Ascites

In adults, intravenous infusion of 8 g of Albumin (Human) 20% may be given for every 1,000 mL of ascitic fluid removed.

Ovarian Hyperstimulation Syndrome

In adults, as a guideline, doses of 50 – 100 g of Albumin (Human) 20% should be infused over 4 hours and repeated at 4- to 12-hour intervals as necessary, when infusion of normal saline fails to achieve or maintain hemodynamic stability and urine output. [ 7 ]

Adult Respiratory Distress Syndrome (ARDS)

In adults, a dose of 25 g of Albumin (Human) 20% can be infused over 30 minutes and repeated at 8 hour intervals for 3 days, if necessary. [ 5 ]

Induction of Diuresis in Patients with Acute Nephrosis

In adults, a dose of 25 g of Albumin (Human) 20% can be infused, administered with an appropriate diuretic once a day for 7 to 10 days.

Hemolytic Disease of the Newborn

In newborns, Albumin (Human) 20% may be administered prior to or during exchange transfusion at a dose of 1 g per kilogram body weight. [ 6 ]

Administration

Intravenous use only.

Prior to administration, parenteral drug products should be inspected visually for turbidity and discoloration, whenever solution and container permit.

Do not dilute with sterile water for injection.

Do not use solutions of Albumin (Human) 20% which are cloudy or have deposits. Once the infusion container has been opened the contents should be used immediately. Discard the unused portion. Filtration of Albumin (Human) 20% is not required.

The infusion rate should be adjusted according to the individual circumstances and the indication. In plasma exchange during paracentesis, the infusion rate may be higher and should be adjusted to the rate of removal.

If large volumes (greater than 1500 ml) are administered, the product should be warmed to room temperature before use.

Dosage Forms and Strengths

Albumin (Human) 20% is supplied in

10 g in 50 mL infusion bottle

20 g in 100 mL infusion bottle

Do not use in individuals who are hypersensitive to albumin preparations, any ingredient in the formulation, or components of the container.

Warnings and Precautions

Hypersensitivity

Hypersensitivity or allergic reactions have been observed, and may in some cases progress to severe anaphylaxis. Epinephrine should be available immediately to treat any acute hypersensitivity reaction.

Hypervolemia/Hemodilution

Hypervolemia may occur if the dosage and rate of infusion are not adjusted to the patient’s volume status. At the first clinical signs of possible cardiovascular overload, e.g., headache, dyspnea, increased blood pressure, jugular venous distention, elevated central venous pressure, pulmonary edema, the infusion should be stopped immediately and the patient reevaluated. Albumin should be used with caution in conditions where hypervolemia and its consequences or hemodilution could represent a special risk for the patient. Examples of such conditions are:

Decompensated cardiac insufficiency

Hypertension

Esophageal varices

Pulmonary edema

Hemorrhagic diathesis

Severe anemia

Renal and post-renal anuria.

20-25% Albumin (Human) is relatively low in electrolytes compared to the 4-5% Albumin (Human) solutions. When albumin is given, monitor the electrolyte status of the patient and take appropriate steps to restore or maintain the electrolyte balance.

Coagulation Abnormalities

If comparatively large volumes are to be replaced, monitoring of coagulation and hematocrit is necessary. Ensure adequate substitution of other blood constituents (coagulation factors, electrolytes, platelets and erythrocytes).

Laboratory Monitoring

If Albumin (Human) 20% is to be administered, monitor hemodynamic performance regularly; this may include:

Arterial blood pressure and pulse rate

Central venous pressure

Pulmonary artery occlusion pressure

Urine output

Electrolytes

Hematocrit/hemoglobin.

Albumin (Human) 20% must not be diluted with sterile water for injection as this may cause hemolysis in recipients.

Infection Risk from Human Plasma

This product is a derivative of human plasma. Based on effective donor screening and product manufacturing processes it carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob Disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have been identified for Albumin (Human) 20%.

Adverse Reactions

General

Adverse reactions for Albumin (Human) 20% normally resolve when the infusion rate is slowed down or the infusion is stopped. In case of severe reactions, the infusion should be stopped and appropriate treatment should be initiated.

Clinical Studies Experience

No clinical studies were done using Albumin (Human) 20%

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Albumin (Human) (any strength). Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency.

Drug Interactions

No drug interaction studies have been conducted.

USE IN SPECIFIC POPULATIONS

Pregnancy

Pregnancy Category C. Animal reproduction studies have not been performed with Albumin (Human) 20%. It is also not known whether Albumin (Human) 20% can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Albumin (Human) 20% should be given to a pregnant woman only if necessary.

Labor and Delivery

It is also not known whether Albumin (Human) 20% can cause fetal harm when administered to a woman during labor or delivery of if it will affect reproductive capacity. Albumin (Human) 20% should be given during labor or delivery only if necessary.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Albumin (Human) 20% should be given to nursing mothers only if necessary. Because many drugs are excreted in human milk, caution should be exercised when Albumin (Human) 20% is administered to a lactating woman.

Pediatric Use

Data on the use of Albumin (Human) 20% in children including premature babies are very limited. The product should be administered to pediatric patients only if needed.

Geriatric Use

Clinical studies did not include a sufficient number of subjects aged 65 and older to determine whether they respond differently from younger subjects.

Albumin (Human) Description

Albumin (Human) 20% is a sterile, liquid preparation of albumin derived from large pools of human plasma. All units of human plasma used in the manufacture of Albumin (Human) 20% are provided by FDA approved blood establishments only.

The product is manufactured by cold ethanol fractionation followed by ultra- and diafiltration. The manufacturing process includes final container pasteurization and additional bulk pasteurization at 60 +/- 0.5°C for 10 – 11 hours. The Albumin (Human) 20% manufacturing process provides a significant viral reduction in in vitro studies (table 2). These reductions are achieved through a combination of process steps including Cohn fractionation and final container pasteurization.

No procedure, however, has been shown to be completely effective in removing viral infectivity from derivatives of human plasma.[see Warnings and Precautions, Infection Risk from Human Plasma (5.7)]

Albumin (Human) 20% is a clear, slightly viscous liquid; it is almost colorless or slightly yellow or green.

The composition of Albumin (Human) 20% is as follows:

Component

Quantity/1000 ml

Protein, of which greater than or equal to

96% is human albumin

200 g

Sodium

130 – 160 mmol

Potassium

less than or equal to 2 mmol

N-acetyl-DL-tryptophan

0.064 - 0.096 mmol/g protein

Caprylic acid

0.064 - 0.096 mmol/g protein

Water for Injection

ad. 1000 ml

Albumin (Human) 20% contains no preservatives and components used in its packaging are latex-free.

Albumin (Human) - Clinical Pharmacology

No pharmacokinetic or pharmacodynamic studies with Albumin (Human) 20% have been conducted.

Mechanism of Action

Albumin is responsible for 75-80% of the colloid osmotic pressure of normal plasma. Albumin stabilizes circulating blood volume and is a carrier of hormones, enzymes, medicinal products and toxins. [ 3 ]

Albumin is a protein with a total extravascular mass of approximately 160 g and an intravascular mass of about 120 g. [ 3 ]

Pharmacodynamics

The colloid osmotic effect of Albumin (Human) 20% and 25% is approximately 5 times the volume administered. When injected intravenously, it will increase circulating plasma volume by approximately 3.5 times the volume infused within 15 minutes if the patient is adequately hydrated. This extra fluid reduces hemoconcentration and blood viscosity. The degree and duration of volume expansion depends upon the initial blood volume. When treating patients with diminished blood volume, the effect of infused albumin may persist for many hours. The hemodilution lasts for a shorter time when albumin is administered to individuals with normal blood volume. [ 4 ]

NON-CLINICAL TOXICOLOGY

No non-clinical toxicology studies with Albumin (Human) 20% have been conducted. Human Albumin is a normal constituent of human plasma and acts like physiological albumin.

Inform patients that Albumin (Human) 20% is a derivative of human plasma and may contain infectious agents that cause disease (e.g., viruses, and theoretically, CJD agent). Inform patients that the risk that Albumin (Human) 20% may transmit an infections agent has been reduced by screening plasma donors for prior exposure for certain viruses, by testing the donated plasma for certain virus infections and by inactivating and/or removing certain viruses during manufacturing [see Warnings and Precautions (5.7)].